1105712-07-9Relevant academic research and scientific papers
Discovery of N-Substituted 3-Amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic Acids as Highly Potent Third-Generation Inhibitors of Human Arginase i and II
Van Zandt, Michael C.,Jagdmann, G. Erik,Whitehouse, Darren L.,Ji, Minkoo,Savoy, Jennifer,Potapova, Olga,Cousido-Siah, Alexandra,Mitschler, Andre,Howard, Eduardo I.,Pyle, Anna Marie,Podjarny, Alberto D.
, p. 8164 - 8177 (2019/10/02)
Recent efforts to identify new highly potent arginase inhibitors have resulted in the discovery of a novel family of (3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid analogues with up to a 1000-fold increase in potency relative to the current standards, 2-amino-6-boronohexanoic acid (ABH) and N-hydroxy-nor-l-arginine (nor-NOHA). The lead candidate, with an N-2-amino-3-phenylpropyl substituent (NED-3238), example 43, inhibits arginase I and II with IC50 values of 1.3 and 8.1 nM, respectively. Herein, we report the design, synthesis, and structure-activity relationships for this novel series of inhibitors, along with X-ray crystallographic data for selected examples bound to human arginase II.
A new family of 1,2,3-oxathiazolidine-2,2-dioxide phosphonate derivatives: Synthesis, characterization and anticancer evaluation
K'tir, Hacène,Aouf, Zineb,Souk, Tan Otea,Zerrouki, Rachida,Berredjem, Malika,Aouf, Nour-Eddine
, p. 555 - 559 (2017/05/01)
An efficient synthesis of a new series of organophosphorus compounds having a cyclic sulfamidates moiety is described. The cyclic sulfamidate precursors were prepared from α-amino acids after four steps (Reduction, N-Boc protection, cyclization and cleavage). The novel organophosphonates were synthesized within two steps starting from the cyclic sulfamidate (chloroacetylation following by phosphorylation via Arbuzov reaction). A particular compound 7-a (diethyl phosphonate {2-[(4S)-4-benzyl-1,2,3-oxathiazolidin-3-yl-2,2-dioxyde]-2-oxoethyl}) was essayed for their in vitro cytotoxic activities against a panel of four cell lines (Jurkat, K562, U266, and A431). For all of these cells, the synthesized compound showed low cytotoxicity, even at high concentration levels (4?mM).
Nucleophilic Trifluoromethylthiolation of Cyclic Sulfamidates: Access to Chiral β- And γ-SCF3 Amines and α-Amino Esters
Zeng, Jun-Liang,Chachignon, Hélène,Ma, Jun-An,Cahard, Dominique
, p. 1974 - 1977 (2017/04/27)
The regio- and stereoselective ring opening of 1,2- and 1,3-sulfamidates with trifluoromethanethiolate anion is reported. This direct introduction of the whole SCF3 motif is a straightforward synthetic route toward β- and γ-SCF3 amines and α-amino acid derivatives. The utility of this reaction was further illustrated by incorporation of Cys(S-CF3) into di- and tripeptides.
Ionic liquid crystals derived from amino acids
Mansueto, Markus,Frey, Wolfgang,Laschat, Sabine
supporting information, p. 16058 - 16065 (2014/04/03)
Novel chiral amino acid derived ionic liquid crystals with amine and amide moieties as spacers between the imidazolium head group and the alkyl chain were synthesised. The key step in the synthesis utilised the relatively uncommon SO3 leaving group in a microwave-assisted reaction. The mesomorphic properties of the mesogens were determined by differential scanning calorimetry (DSC), polarising optical microscopy (POM) and X-ray diffraction. All liquid crystalline salts exhibit a smecticA mesophase geometry with strongly interdigitated bilayer structures. An increase of the steric bulk of the stereogenic centre hindered the formation of mesophases. In case of phenylalanine-derived derivatives a mesomorphic behaviour was observed for shorter alkyl chains as compared to other amino acid derivatives indicating an additional stabilising effect by the phenyl moiety. Ionic liquid crystals from amino acids: Novel chiral amino acid derived imidazolium salts with amine or amide units were prepared through the sulfamidate. Depending on the steric bulk of the R group, the chain lengths and the type of anion X, stable SmA phases were detected (see scheme; Bn=benzyl). Copyright
Catalytic asymmetric alkylation reactions for the construction of protected ethylene-amino and propylene-amino motifs attached to quaternary stereocentres
Moss, Thomas A.,Barber, David M.,Kyle, Andrew F.,Dixon, Darren J.
supporting information, p. 3071 - 3081 (2013/03/28)
An efficient catalytic and stereoselective method for the direct construction of protected ethylene-amino and propylene-amino scaffolds attached to quaternary stereocentres is reported. Preliminary investigations revealed a mild base catalysed nucleophilic ring opening of N-sulfonyl aziridines using the commercially available phosphazene base 2-tert-butylimino-2-diethylamino-1,3- dimethyl-perhydro-1,3,2-diazaphosphorine (BEMP) was possible and resulted in highly efficient alkylation reactions with a range of methine carbon acids. This reaction could be rendered highly asymmetric (up to 97 % ee) by employing phase-transfer catalysis to control stereoinduction. Incorporation of alkyl substituents onto the aziridine electrophile, resulted in a highly diastereoselective (up to 30:1 d.r.) variant of this methodology. A further extension using N-protected cyclic sulfamidates as the electrophilic component was successful with a range of pro-nucleophiles (up to 96 % ee and 45:1 d.r.) and allowed a range of nitrogen protecting groups (carbamate, sulfonyl, phosphonyl, benzyl) to be incorporated into the alkylation adducts. Finally, the utility of the products have been demonstrated in the synthesis of useful heterocycles and compounds bearing structural components of natural products. Open sesame: The enantio- and diastereoselective nucleophilic ring opening of protected aziridines and cyclic sulfamidates using asymmetric phase-transfer catalysis (PTC) is reported. The ring-opening alkylation reactions create quaternary chiral centres containing ethylene- and propylene-amino motifs in good yields with good to excellent enantioselectivities (see scheme). These reactions are broad in scope and a wide range of pro-nucleophiles are tolerated. Copyright
Chiral dihydrobenzo[1,4]oxazines as catalysts for the asymmetric transfer-hydrogenation of α,β-unsaturated aldehydes
Ebner, Christian,Pfaltz, Andreas
, p. 10287 - 10290 (2012/02/01)
A new class of organocatalysts based on the structure of 2,3-dihydrobenzo[1,4]oxazine was prepared and applied in the enantioselective transfer-hydrogenation of α,β-unsaturated aldehydes with Hantzsch ester as hydride donor. These catalysts proved to be particularly effective for the conjugate reduction of β,β-diaryl-substituted acrylaldehydes leading to saturated aldehydes bearing a stereogenic center with two different aryl groups with enantioselectivities of up to 91% ee.
